Copy number and gene expression alterations in radiation-induced papillary thyroid carcinoma from chernobyl pediatric patients.

BACKGROUND

Following exposure to radiation during the Chernobyl fallout tragedy, papillary thyroid carcinoma (PTC) increased significantly in individuals who were children at the time of the accident. We have used two high-throughput, whole genome platforms to analyze radiation-induced PTCs from pediatric patients from the Chernobyl region.

METHODS

We performed comparative genomic hybridization using Affymetrix 50K Mapping arrays and gene expression profiling on 10 pediatric post-Chernobyl PTCs obtained from patients living in the region. We performed an overlay analysis of these two data sets.

RESULTS

Many regions of copy number alterations (CNAs) were detected including novel regions that had never been associated with PTCs. Increases in copy numbers were consistently found on chromosomes 1p, 5p, 9q, 12q, 13q, 16p, 21q, and 22q. Deletions were observed less frequently and were mapped to 1q, 6q, 9q, 10q, 13q, 14q, 21q, and 22q. Gene expression analysis revealed that most of the altered genes were also perturbed in sporadic adult PTC; however, 141 gene expression changes were found to be unique to the post-Chernobyl tumors. The genes with the highest increases in expression that were novel to the pediatric post-Chernobyl tumors were TESC, PDZRN4, TRAa/TRDa, GABBR2, and CA12. The genes showing the largest expression decreases included PAPSS2, PDLIM3, BEXI, ANK2, SORBS2, and PPARGCIA. An overlay analysis of the gene expression and CNA profiles was then performed. This analysis identified genes showing both CNAs and concurrent gene expression alterations. Many of these are commonly seen in sporadic PTC such as SERPINA, COL8A, and PDX, while others were unique to the radiation-induced profiles including CAMK2N1, AK1, DHRS3, and PDE9A.

CONCLUSIONS

This type of analysis allows an assessment of gene expression changes that are associated with a physical mechanism. These genes and chromosomal regions are potential markers for radiation-induced PTC.